Arctigenin (ATG) is the main monomer compounds in a Chinese traditional medicine named fructus arctii. Fructus arctii is widely used in the treatment of diabetes in clinical, but its mechanism of action and the effective composition is not clear. In this disclosure, the study found that the ATG significantly reduce proteinuria in diabetic mice.
PP2A is a serine threonine phosphorylase that regulates most of the phosphorylases in eukaryotic cells. In the signal transduction cascade, PP2A interacts with other phosphorylase and kinase, constitute macromolecule for the regulation of downstream signal transduction. In diabetic kidney disease (DKD) P65 is the key pathway leading to inflammation. PP2A can dephosphorylate P65 and thereby plays the role of treating the DKD. In addition, there are studies revealing that PP2A and proto-oncogene c-Myc are closely linked. The PP2A's regulatory subunit B56α selectively binds to the N-terminus of c-Myc, resulting in a significant reduction in c-Myc expression levels. Using shRNA to release the binding of B56α to c-Myc can lead to the overexpression of c-Myc, thus increasing the c-Myc Ser62's phosphorylation level and the enhancement of c-Myc's function and other similar phenomina. According to this, it is easy to conjecture that PP2A plays a key role in the regulation of cell proliferation and differentiation.
The clinical manifestations of diabetic nephropathy were persistent increasing of proteinuria and decreasing of glomerular filtration rate. The 24-hour total proteinuria of normal adult is less than 150 mg, and adolescents can be slightly higher but not more than 300 mg/24 h. When the total protein in the urine exceeded 300 mg/24 h was detected, that is known as proteinuria. Proteinuria is the most serious problem in patients with diabetic nephropathy, urinary protein content is not only related to the degree of renal damage, but also one of the main indicators of determining the progress of diabetic patients with chronic kidney disease. Urine of normal human contains very small amounts of protein, their urine protein is negative in routine examination. However, if the glomerular structure changes caused by renal disease, resulting in increasing glomerular filtration membrane permeability, it would make the protein in glomerular filtrate increased and beyond the renal tubular reabsorption capacity, thereby appears the proteinuria, in which the protein is mainly albumin. 24 hour urine albumin between 30-300 mg/24 h is referred as microalbuminuria which is an indicator of early diabetic nephropathy. Lowering proteinuria may reduce its continued damage to the kidneys.
Arctigenin (ATG) has a variety of biological activities. However, as a potential drug, even if it has a significant effect, in order to carry out a wide range of applications, as well as to improve the practical effect on the human body, it still needs further improvement. Natural ATG has the characteristics of low water solubility and easy decomposition in primary metabolites, which limits its further application. Therefore, how to improve the effect of the natural product ATG has become an urgent problem to be solved in the art.